7-94398387-T-C

Position:

chr7-94398387-T-C

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The ENST00000297268.11(COL1A2):c.87T>C(p.Thr29=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0398 in 941,242 control chromosomes in the GnomAD database, including 4,186 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.12 ( 2768 hom., cov: 32)

Exomes 𝑓: 0.024 ( 1418 hom. )

Consequence

COL1A2
ENST00000297268.11 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 1.88

Variant links:

Genes affected

COL1A2 (HGNC:2198): (collagen type I alpha 2 chain) This gene encodes the pro-alpha2 chain of type I collagen whose triple helix comprises two alpha1 chains and one alpha2 chain. Type I is a fibril-forming collagen found in most connective tissues and is abundant in bone, cornea, dermis and tendon. Mutations in this gene are associated with osteogenesis imperfecta types I-IV, Ehlers-Danlos syndrome type VIIB, recessive Ehlers-Danlos syndrome Classical type, idiopathic osteoporosis, and atypical Marfan syndrome. Symptoms associated with mutations in this gene, however, tend to be less severe than mutations in the gene for the alpha1 chain of type I collagen (COL1A1) reflecting the different role of alpha2 chains in matrix integrity. Three transcripts, resulting from the use of alternate polyadenylation signals, have been identified for this gene. [provided by R. Dalgleish, Feb 2008]

COL1A2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.69).

BP6

Variant 7-94398387-T-C is Benign according to our data. Variant chr7-94398387-T-C is described in ClinVar as [Benign]. Clinvar id is 196205.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-94398387-T-C is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=1.88 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.348 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COL1A2	NM_000089.4 linkuse as main transcript	c.87T>C	p.Thr29=	synonymous_variant	3/52	ENST00000297268.11	NP_000080.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COL1A2	ENST00000297268.11 linkuse as main transcript	c.87T>C	p.Thr29=	synonymous_variant	3/52	1	NM_000089.4	ENSP00000297268	P1

Frequencies

GnomAD3 genomes

AF:

0.121

AC:

18400

AN:

151776

Hom.:

2762

Cov.:

show subpopulations

Gnomad AFR

AF:

0.331

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0764

Gnomad ASJ

AF:

0.0141

Gnomad EAS

AF:

0.362

Gnomad SAS

AF:

0.0710

Gnomad FIN

AF:

0.0315

Gnomad MID

AF:

0.0362

Gnomad NFE

AF:

0.0107

Gnomad OTH

AF:

0.102

GnomAD3 exomes

AF:

0.0590

AC:

10069

AN:

170612

Hom.:

1133

AF XY:

0.0527

AC XY:

4947

AN XY:

93832

show subpopulations

Gnomad AFR exome

AF:

0.316

Gnomad AMR exome

AF:

0.0550

Gnomad ASJ exome

AF:

0.0135

Gnomad EAS exome

AF:

0.322

Gnomad SAS exome

AF:

0.0499

Gnomad FIN exome

AF:

0.0296

Gnomad NFE exome

AF:

0.00948

Gnomad OTH exome

AF:

0.0385

GnomAD4 exome

AF:

0.0240

AC:

18983

AN:

789352

Hom.:

1418

Cov.:

AF XY:

0.0243

AC XY:

9837

AN XY:

404674

show subpopulations

Gnomad4 AFR exome

AF:

0.259

Gnomad4 AMR exome

AF:

0.0517

Gnomad4 ASJ exome

AF:

0.0116

Gnomad4 EAS exome

AF:

0.229

Gnomad4 SAS exome

AF:

0.0471

Gnomad4 FIN exome

AF:

0.0242

Gnomad4 NFE exome

AF:

0.00651

Gnomad4 OTH exome

AF:

0.0372

GnomAD4 genome

AF:

0.121

AC:

18451

AN:

151890

Hom.:

2768

Cov.:

AF XY:

0.122

AC XY:

9087

AN XY:

74242

show subpopulations

Gnomad4 AFR

AF:

0.331

Gnomad4 AMR

AF:

0.0763

Gnomad4 ASJ

AF:

0.0141

Gnomad4 EAS

AF:

0.362

Gnomad4 SAS

AF:

0.0704

Gnomad4 FIN

AF:

0.0315

Gnomad4 NFE

AF:

0.0107

Gnomad4 OTH

AF:

0.107

Alfa

AF:

0.0264

Hom.:

373

Bravo

AF:

0.136

Asia WGS

AF:

0.242

AC:

828

AN:

3414

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Nov 17, 2015	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 01, 2016	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Sep 27, 2012	- -

Osteogenesis imperfecta

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Ehlers-danlos syndrome, arthrochalasia type, 2

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Osteogenesis imperfecta type I;C0268335:Ehlers-Danlos syndrome, classic type, 1

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

Cardiovascular phenotype

Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 04, 2019

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.69

CADD

Benign

DANN

Benign

0.77

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over